Manufacture of nu-tertiary amino acyclic carboxylic acids and their salts



Pmma June 0, 1940 UNITED; STATES mum-scrum or N 'rnn'rmar sum AOYCLIC OARBOXYLIC ACIDS AND THEIR I William Stansiield Calcott, Woodstown, Donia Spiegler, Woodbury, and John Carney: Point, N. .L, assignors Marlin Tinker, to E. l. du Pont de Nemonrs & Company, Wilmington, Del., a corporation of Delaware 14 Claims.

7 This invention relates to the production of ;N-tertiary amino acyclic carboxylic acids of the general formula: v

in which R, A, and A represent hydrogenor alkyl radicals having from 1v to 20 carbon atoms, ,R' and R" are alkyl groups containing from 1 to 5 carbon atoms, and n denotes 0, 1, or 2. More particularly, this invention relates to the process of preparing the above-described tertiary amino carboxylic acids throughthe condensation of (a) ll anhydrous aliphatic amines oi thetype (where R and R." represent allrvl radicals of the formula CaHZa-H; i. e., CH4, CaHs, CaH1,.etc., in

which ii tands for a number not greater than 5) in the resenee or absence of a tertiary allphatic amine oi the type:

m where R, iii, andit'" are aikyl radicalsoi the formula 0.11: in which n is a number not greater than 4, with '(b) halogen substituted acyclic carboxylic acids of the general formula:

, wherein x stands for a halogen atom,"R, A, and o A are hydrogen or alkyl radicals having from 1 to 20 carbon atoms, and n denotes o, 1, or 2.

This invention also relates to a process of vpreparing the above-described N-dialkyl amino carboxylic acids from a'mlxture oi a dialkyl amine and a trialkyl amine by condensation with a halogen substituted acyclic carboxylic acid (as indicated above) in such a manner as to separate the trialkyl amine from the dialkyl amine in essentially pure iorm.

This invention also relates to the production of a number of N-tertiary amino carboxylic acids which are new chemical compounds. These are obtained by the above-mentioned process which will be more fully described hereinafter. I" An ohiect oi this invention is to provide a No Drawing. Application August 28, 1937,

, Serial No. 161,022

- novel and easily conducted process (or the production of N-dialkyl amino carbogwiic acids which employs relatively inexpensive starting materials and gives high yields of products of good quality.

Another object process for the preparation of pure dialkyl amino carboxylic acids from commercial binary mixtures of secondary and tertiary aliphatic amines which are cheaply obtainable through the reaction of aliphatic alcohols with ammonia.

while preparing a pure dialkyl amino carboxylic acid, a novel method for the separation 01 a binary mixture of a dialkyl amine and a trialkyl amine into its components.

A still further object is the production of a number of new and valuable chemical com pounds. -More specifically, the invention involves the production of the following new compounds:

Name Formula of this invention is to provide a Y A further object of this invention is to provide, 7

N-di-n-hutyl amino acetic acid.

( iHil)lNgg|00oH 1 (2; N-di-amyl amino acetic acid.-- a) N-alpha-di-n-butyl mums pro (0H0)|N-IH C 0 OH (4) -b0ta-dl-n-butyl amino proplonic acid 'These objects are accomplished by the following invention which comprises reacting under non-aqueous conditions halogen substituted acy clic carboxylic acids with anhydroussecondary aliphatic amines alone or in admixture with tertiary aliphatic amines. There is obtained when using a halogen substituted carboxylic acid and a mixture of anhydrous secondary and tertiary aliphatic amines for reaction as above: (I) a dialkyl amino carboxylic acid fixed as the salt of a dialkyl amine, (II) a dialkyl amine hydrohalide, and (III) .unreacted trialkyl amine. (I) and (II) are precipitated out as asemi-crystalline solid while (111) separates out as an oil layer. The anhydrous trialkyl amine (separated from dialkyl amine bythe condensation) can be isolated by decantation or distillation procedures. The fixed dialkyl amine salts (I) and (II) are reacted with aqueous alkali to liberate a purified dialkyl amine (containing relatively negligible quantities of triallryl a me), which can be recovered by distillation. The residual mass contains the sodium salt of the desired dialkyl amino carboxylic acid and a sodium halide. If desired, these can be separated by crystallization methods. The following equations represent the re- The following examples in which parts are given by weight illustrate but do not limit theinvention.

. EXAMPLE 1 N-dimethyl glycine rr-omooon A mixture of dimethyl amine and trimethyl amine of binary composition which analyzes 61.7% dimethyl amine, 37.5% trimethyl amine 480 parts of a binary mixture containing 29'7- parts of dimethtyl amine and parts of tri-- methyl amine are, cooled to -10 0. While agitating, the parts of chloro-acetic acid are added thereto in small portions over a period of 3 to 4 hours while keeping the temperature at -'7.5 to 10 C. by external cooling. At the completion of the reaction, which requires from 1 to 2 hours, there is observed upon settling a two layer system, namely a clear upper layer, and a thick semi-solid crystalline lower layer. 'The clear upper layer is practically pure trimethyl amine which can be separated by d'ecantatlon, filtration, or distillation methods. The separated product boils at 3.74 C. and analyzes 99.25% as trimethyl amine. When mixed with aceticv acid and acetic anhydride, the mixture shows no heat rise indicating the absence of dimethyl amine.

160 parts of sodium hydroxide dissolved in 500 parts of water are used to causticize the residualcrystalline mass which consists of dimethyl amine hydrochloride and the dimethyl amine salt of dimethyl glycine. The reaction with alkali liberates dimethyl amine as a vapor which can be absorbed in water or condensed to yield an anhydrous product which boils at 7 C. and which analyzes 92-93% dimethyl amine, 0.25-0.5% monomethyl amine, and 5 5% of trimethyl amine. The reactions involved in the above'procedure 'may be illustrated by the following equations.

The residual still liquors contain sodium di methyl glycinate and sodium chloride. For many purposes where the presence of salt and water is 33% sodium chloride, as normally obtained by evaporation of the reaction mixture, when recrystallized twice from 4 to 5 parts of 90% ethyl alcohol to eliminate insoluble sodium chloride,

- ,yields practically pure sodium dimethyl glycinate.

Analysis Calculated for Fmmd C4H OiNNa Percent nitrogen 11:0 11. 2 Percent NaCl 0. 0 0.0

For most practical uses, the dimethtyl glycine i can be employed as the sodium salt. If, however,

the free amino acid is desired, it can be readily obtained by dissolving the sodium salt in hot absolute ethyl or methyl alcohol followed by careful acidification with a weighed theoretical quantity of hydrochloric acid as gas or concentrated solution. This precipitates sodium chloride and leaves dimethyl glycine dissolved in the alcohol. Evaporation of .the alcoholic solution results in the desired dimethyl glycine as the free amino acid. I

The dimethyl glycine can also be isolated as the hydrochloride by treatment of the condensation mass with barium hydroxide, evaporation to small volume, and precipitation through addition of alcohol'and concentrated hydrochloric acid.

A Analysis Calculated for Fmmd crnmolNoi Percent chlorine 0 25. 3 2 5. 4 Percent nitrogen l0. 0 9. 9B Melting range, C 192-194 Pure anhydrous dimethyl amine may be used in place of the anhydrous binary mixture of dimethyl amine and trimethyl amine in the reaction described in this example. I

The above-described reaction is not confined only to chloro-acetic acid. Other halogeno substituted acetic acids such as iodo-, bromo-, or fluoro-acetic acid may be employed. The following example indicates the reaction of iodo-acetic =acid (ICH2COOH) and anhydrous dimethyl amine.

EXAMPLE 2 in Example 1. To obtain pure sodium dimethyl u zene, or ligroin.

glycinate, the sodium iodide can be removed irom the dried crude product either by extraction with or recrystallization from 90-95% ethyl alcohol.

The reaction is general in that it can be ap-' plied to alpha halogen substituted homologues of acetic acid. Examples 3, 4, and 5 illustrate the application with reference to anhydrous dimethyl amine and alpha halogen substituted propionic, butyric, and stearic acids.

Exurrrr: 3 Alpha N-dimethul amino propionic acid Caron-coon CH: CH:

100 parts of anhydrous dimethyl amine are condensed at -5 C. to C. with 33 parts of alpha chloroproplonic acid (CHsCHClCOOH).

The excess oi anhydrous dimethyl amine is recovered by distillation procedure. Dilution with l00parts of water and alkalization with 24 parts of caustic, soda (NaOI-I) dissolved in'36 parts of water liberates the fixed dimethyl amine. The aqueous solution upon evaporation to dryness yields 60.5 parts (100% of'theory) oi! a mixture of 18 parts of sodium chloride and 42.5 parts of the v F sodium salt of alpha dimethyl amino propionic acid. This mixture can be'separated 'by extrac: tion with absolute ethyl alcohol, which leaves sodium chloride undissolved. The purified sodiumsalt of alpha dimethyl amino propionic acid is obtained upon evaporation of the alcohol solution. It can also be precipitated from the alcohol solution by addition of 6-'7- volumes of acetone. In this manner, there' is obtained in good yield thecolorless sodium salt which is soluble in water and ethyl alcohol but insoluble in acetone, ben- Analysis Calculated for mmd oral-0mm Percent nitro on 0. 71 10.06 Percent chlor no 0. 50 0. 00

Exsurnn 4 a 7 .Alpha N-dimethul amino butyric acid cmc'ur-om-coon CH: CH:

'100 parts of anhydrous dimethyl amine are stirred at 1 to 0 C. with 51 parts of alpha bromo-butyric acid.. The reaction is complete By treatment with enough caustic soda to liberate the fixed amine andto 'form the sodium salt of the carboxylic acid' there is obtained upon'evaporation, a solid mixture 'oi' "sodium bromide and the sodium'salt V of aipha-N-dimethyl amino butyric acid. Precipi tation from an ethyl alcohol solution with ace-' tone, asdesc-ribed in Example 3, yields an essentially pure sodium salt of alpha N-dimethylamino Analysis;

Y commune T, '6'? 'Q i l rmtmafi m. see I an .Percentbroni 0.15 i 0.00

- while holding the temperature under sequent-treatment with water and 12 parts oi! Ermine 4 Alpha N-dimethyl amino stearic acid 135' parts of anhydrous dimethyl amine are cooled 'to 10 0., 88 parts of commercial bro-r minated triple press stearic acidtiwhich-is a mixture of 40% palmitic acidan'd I stearic acid whose. average molecular weight is 349). are

. added in small portions while stirring. Alter lleutrallration Percent Percent equivalent r N 7 Br mg.

KOH/gmw ll ound 4. 47 0. 14 11s. 4 Calculated (for an average molecular weight oi 313).-.. 4.43 0.00 I A 179- In addition to halogenated stearic acid, other long chain halogenated fatty acids may be em ployed such as. those obtained from coconut oil and palm kernel oil. I I v The invention here described is not confined" only to the reaction of anhydrous dimethyl amine with alpha halogen substituted acyclic carboxylic acids, since homologues of dimethyl amine' such as diethyl amine, dipropyl amine, dibutyl amine, and diamyl amine can also be successfully employed, as will be shown in Examples 6 tol2.-

This product is easily obtained by the reactionof anhydrous diethyl amineand bromo-acetlc acid (Br-CHzCOOH). I diethyl amine are cooled to 10C. bromo-acetic acid are added slowlywith stirring C. Sub

caustic soda liberates the fixed diethyl amine and leaves in aqueous solution sodiumbrom ide and sodium diethyl glycinate. The puriiledsm dium salt is readily isolated by procedure such as that described in Examples 3 "and 4.- The parts oi anhydrous 21 partsof' analysis given below indicates the quality or product which is readily obtainable in one crystalliaation from an alcohol and acetone mixture.

Analysis estimate a u |NIfIa Pei-meme: ass out Percentbromne. 1.91 "0.00

Exmul warm-am: dim-in? f I I 20 parts of technically pure product (95.2% purity).

' Analysis Cal ltedi 'Fmmd c..fii.'c .m?

' i 5.0a 6,28 ifif fiifiri' fifi' 1.31 0.00

similarly anhydrous di-n-propyl amine is reacted with chloro-acetic acid to yield N-di-npropyl glycine. 60 parts of di-n-propyl mine are condensed at 5-10 C. with 16 parts ot'chloroacetic acid. Treatment with 12 parts of sodium hydroxide in aqueous solution yields a mixture of sodium chloride and sodium N-di-n-propyl glycinate. Purification to obtain the pure sodium salt, the free acid, or the hydrochloride can be 80 parts of di-n-butyl amine are heated for 8 1 hours at 100 C. with 19.5 parts of alphabromopropionic acid. After treatment with 12 parts of sodium hydroxide and recovery of unreacted di-n-butyl amine by distillation in vacuum, there is obtained upon extraction with diethyl ether,

an ether solution of alpha N-di-n-butyl amino sodium propionate. Evaporation to dryness yields If desired, the product may be further freed from sodium bromide by repeated recrystalliza- 'tions from diethyl ether or ligroin.

EXAMPLE 9 160 parts of di-n-butyl amine are reacted at 35-40 C. When fully reacted after from 3 to 4 hours of stirring, the mass is diluted with 100 parts 01 water in whichhave been dissolved 24 parts of caustic soda. v water at constant volume to recover unreacted dibutyl'amine. The aqueous solution left in the still is clarified by boiling with activated char- I coal followed by filtration through Florida Earth or diatomaceous earth. Evaporation to dryness results in a mixture 01' sodium chloride and sodium dibutyl glycinate. The sodium dibutyl glycinate can be separated from sodium chloride through solution in cold absolute ethyl alcohol. Addition of from 7 to 10 volumes of acetone reprecipitates the sodium dibutyl glycinate as a colorless milklike product, which is 95.5% pure when dried.

Analysis Calculated for ommtomm P tnitr en 6.38 13g P t chlo l ne H 0. 4B 0, on

Exams: 10 v The above-described N-dibutyl glycine can also be prepared from a mixture of dibutyi amine and trlbutyl amine throughreaction at 15-25 C. with chloro-acetic acid. The results are similar to those obtained in Example lwhere a mixture of dimethyl amine and trimethyl amine was Percent nitrogen with 30 parts of chloro-acetic acid.

The mass is then distilled with react, while the-amine which is fixed as salts and the base liberated by essentially pure dibutyl amine. Analysis of d ibutvl amine recovered Calculated :4. Found (0.30MB

10.37 10.86 Bolling range, C 100-162 100 A quantitive yield of the sodium salt of N-di-nbutyl glycine is obtained.

EXAMPLE 11 N-dlamyl glycine (CuHnMN-CHaCOOH,

3 to 4 hours at 5580 C. with 30' parts 01' chloroacetic acid. Treatment with caustic soda solution liberates uncondensed amine, which may be recovered by distillation procedures. evaporation in vacuum sodium N-diamylglycinate in admixture with sodium chloride. Purification of this sodium salt by solution in organic solvents can be eiiected as described in theprevious examples; The bydrochloride is readily obtained through the addition of dry gaseous hydrogen chloride to a solution. of the sodium dlamyl glycinate in absolute ethyl alcohols The hydrochloride o1 'diamyl glycine is extremely soluble in water, acetone, and alcohol. It is insoluble in diethyl ether and ligroin.

Examples 1 to 11 have illustrated the condensation of secondary aliphatic amines with alpha can also be condensed with secondary aliphatic amines, as will be shown by the next two examples.

EXAMPLE 12 Beta N-di-n-butyl amino propionic acid (CiHo) aN-CHsCHzCOOH 30.5 parts of beta BrCHaCHiCOOH) are added in small portions with stirring to 100- parts of di-n-butyl amine. The temperature rises from 20 C. to 40 C. during the addition. After from 1 to 2 hours, the mass is heated to 60 C. and held for 6-7 hours until the reaction is complete. The test for completion is made as follows: A sample of the reaction mass is dissolved in cold water. Inorganic bromides which have been formed are completely precipitated through addition of cold-nitric acid and silver nitrate solution. The clear filtrate (from which silver bromide has been precipitated in the cold) should, upon boiling with more nitric acid and silver nitrate solution, give no further silver bromide precipitation.

Treatment of the finished condensation mass with caustic soda, as described in previous examples, yields, after removal of liberated amine,- a mixture of sodium bromide and sodium beta dibutyl amino propionate in aqueous solution. For purposes of economy, bromine may be distilled and recovered from this solution by treatment with mild oxidizing agents such as alkali hypochlorites, alkali bromates or hydrogen per: oxide. The residual sodium beta dibutyl amino Further yields as solid the desired.

bromo-propionic acidcaustic soda treatment is I halogen substituted acyclic carboxylic acids. J

This invention, however, is not restricted .to re- 10 v tone.

propionate can be isolated by evaporation. If

desired,the product so obtained can be freed from inorganic salts through solution in alcohol or ace- ExAMPLr: 13

Beta N-di methyl amino propionic acid (CH3) 2NCH=CH:COOH

60 parts of beta iodo-propionic (ICH2CH2COOH) are added while stirring in small portions to 100 parts of anhydrous dimethyl amine whose temperature is maintained at 15 to 10 C. Treatment with 24 parts of sodium hydroxide in aqueous solution, and

- evaporation to dryness gives a quantitative yield of sodium iodide, and the sodium salt of dimethyl amino propionic acid. The sodium salt of dimethyl amino propionic acid is soluble in ethyl alcohol, acetone, and water. It is insoluble in hydrocarbons such as benzene, toluene or xy1ene. I

Although specific examples have been given,

- this invention is not limited to them alone, since form.

modifications may be made by those skilled in the art without departing from the scope of this invention. The temperatures and pressuresrequired for the condensations described in the above examples may be varied over a considerable range without seriously affecting the final result. For example, it may be of advantage, in

order to eliminate excessive refrigeration costs when condensing chloro-acetic acid with dimethyl amine or any other low boiling amines, to operate under superatmospheric conditions; i. e., 5-10 atmospheres at relatively elevated temperatures (55-1Q0 0.).

Variations in the proportions of the reactantsused, and in the mode of mixing of the reactants can also be made.

Theseparation of secondary and tertiary aliphatic amines by reaction with a halogen substituted carboxylic acid is not general. It is operable onlyfor the lower homologues; i. e., methyl to butyl amines inclusive. A mixture of diamyl amine and triamyl amine is not suitably separated in this manner.

The sodium salts of N-tertiary amino acyclic carboxylic acids, as for example sodium dimethyl glyclnate and its homologues, have been used for selective removal of hydrogen sulfide from coke oven gases. N-tertiary amino acyclic carboxylic acids have recently been found useful as intermediates in the manufacture of new detergents such as-the The above description and examples are intended to be illustrative only and not to limit' the scope of the invention. Any departure therefrom which conforms to the spirit-of the invenacid tion is intended to be included within the scope of the appended claims.

We claim: I

. 1. A process for the preparation of the sodium salt of N-dimethyl glycine which comprises reacting an undiluted anhydrous binary mixture ofdimethyl'amine and trimethyl amine with chloro-acetic acid at about C., separating trimethyl amine which does not participate in the reaction from the dimethyl amine salts which are formed, reacting the dimethyl amine salts with an aqueous solution of sodium hydroxide to liberate dimethyl amine as a gas andform sodium chloride and the sodium salt of N-dimethyl glycine in water solution, evaporating this solution to dryness, and separating the sodium salt of N-dimethyl glycine from sodium chloride by treatment with 90% ethyl alcohol to eliminate insoluble sodium chloride.

-2. In a process of preparing an N-dialkylamino aliphatic monocarboxylic acid, the step which comprises reacting an anhydrous dialkyl amine wherein the alkyl groups each contain from 1 to 5 carbon atoms with a mono-halogen substituted aliphatic monocarboxylic acid which contains from 2 to 4 carbon atoms under nonaqu'cous conditions and in the absence of or-- amino acyclic carboxylic acid of the general formula:

wherein R'represents a member of the group consisting of hydrogen and alkyl radicals having from 1 to 20 carbon atoms, R and R" stand for alkyl radicals containing from 1 to 5 carbon atoms, and n denotes 0, 1, or 2; the step which comprises condensing in the-absence of water and organic solvents an anhydrous dialkyl amine wherein the alkyl groups each containfrom 1 to 5 carbon atoms with a halogen substituted acyclic carboxylic acid of the general formula:

wherein X stands for a halogen atom, R represents a member of the group consisting of hydrogen and alkyl radicals having from 1 to 20 carbon drochloride and the dimethyl amine salt of N- dimethyl glycinewith an'alkali metal hydroxide to obtain an alkali metal salt of N-dimethyl glycine, dissolving the alkali metal salt of N- dimethyl glycine in hot absolute ethyl alcohol, acidifying said alcohol solution with hydrochloric acid, and separating the alkali metal chloride which precipitate upon acidification from the alcohol solution of N-dimethyl glycine.

8. In a process of preparing N-dimethyl glycine, the steps which comprise condensing a mono halogeno substituted acetic acid with anhydrous dimethyl amine at a temperature below C. in the absence of water and organic solvents, and converting the dimethyl amine salt of N-dimethyl glycine which is thereby obtained to an alkali metal salt of N-dimethyl glycine by reaction with an alkali metal hydroxide.

9. In a process of manufacturing an alpha N- dimethyl amino monocarboxylic acid which contains from 4 to 6 carbon atoms, the steps which comprise condensing anhydrous dimethyl amine with an alpha halogen substituted monocarboxylic acid which contains from 2 to 4 carbon atoms in the absence of water and organic solvents, and converting the dimethyl amine salt of the N-dimethyl amino monocarboxylic acid which is thereby obtained to an alkali metal salt of an alpha N-dimethyl amino monocarboxylic acid by reaction with an alkali metal hydroxide.

10. In a process of preparing an N-dialkyl glycine wherein each of the alkyl groups contains from 1 to carbon atoms, the steps which comprise, condensing a mono halogeno substituted acetic acid with an anhydrous dialkyl amine in which each of the alkyl groups contains from 1 to 5 carbon atoms in the absence of water and organic solvents, and converting the dialkyl amine salt of an N-dialkyl glycine which is thereby obtained to an alkali metal salt of an N-dialkylglycine by reaction with an alkali metal hydroxide.

11. In, a process of preparing an N-dialkyl amino monocarboxylic acid in which each of the alkyl groups contains from '1 to 5 carbon atoms and the monocarboxylic acid radical contains from 2 to 4 carbon atoms, the steps which comprise condensing an anhydrous dialkyl amine wherein each of the alkyl groups contains from 1 to 5 carbon atoms with a mono halogen substituted monocarboxylic acid which contains from 2 to 4 carbon atoms in the absence of water and organic solvents,fand converting the dialkyl amine salt of an N-dialkyl amino monocarboxylic acid which is thereby obtained to an alkali metal salt, of an N-dialkyl amino monocarboxylic acid by reaction with an alkali metal hydroxide.

12. A process for the preparation of the sodium salt of N-dimethyl glycine which comprises condensing mono chloro-acetic acid with anhydrous dimethyl amine in the absence of water and organic solvents, and converting the dimethyl amine salt of N-dimethyl glycine which is thereby obtained to the sodium salt of N -dimethyl glycine by reaction with sodium hydroxide.

13. In a process for preparing N--dibutylv glycine, the steps which comprise condensing anhydrous di-n-butyl amine with chloro-acetic acid in the absence of water and organic solvents, and

converting the dibutyl amine salt of N-dibutyl glycine which is thereby obtained to the sodium salt of N-dibutyl glycine by reaction" with sodium hydroxide.

14. In a process for preparing N-diamyl glycine, the steps which comprise condensing anhydrous diamyl amine with chloro-acetic acid in the absence of water and organic solvents, and converting the diamyl amine salt of N-diamyl glycine which is thereby obtained to the sodium salt of N-diar'nyl glycine by reaction with sodium hydroxide.

. WILLIAM STANSFIELD 'CALCOTI.

LOUIS SPIEGLER. JOHN MARLIN TINKER. 

